Current potency tests for inactivated poliovirus vaccine (IPV) measure antigen (Ag) content in vitro or serum neutralizing antibody (NAb) responses in animals. The recent establishment of transgenic (Tg) mouse strains carrying the gene for the human poliovirus receptor (PVR) allowed investigation of the correlation of potency tests with protection against disease caused by poliovirus. Studies conducted at LMD with IPV and a Type 3 wild poliovirus strain have found that protection against lethal challenge was induced by IPV in the Tg PVR mouse model, NAb level correlated with protection, varied vaccination and challenge regimens differed in protective effect, and poliovirus C Ag did not induce protection. Administration of immune mouse serum conferred passive immunity at NAb levels corresponding to those obtained by protective immunization of Tg mice with IPV, indicating a dominant role for humoral immunity in IPV mediated protection. Trivalent IPV was less protective than monovalent IPV administered at the same doses. The Tg PVR mouse protection test may have applications to important questions surrounding the adoption of new immunization protocols of combined vaccines containing IPV, and the efficacy of vaccine regimens involving sequential administration of IPV and OPV.